The objectives of this project are to investigate by "in vivo" microscopy, histochemistry, electronmicroscopy, and concomitant hematologic, physiological, and biochemical methods the mechanisms by which the hemopoietic microenvironment may influence or regulate the production, maturation, and release of erythroid cells using as an aid in evaluating these mechanisms various known stimulators and inhibitors of erythropoiesis. This will be accomplished by studying experimental conditions of erythropoietic stimulation or suppression produced by chemicals, hypoxia, irradiation, or genetic defects in order to: (1) determine the cell(s) responsible for microvascular dilatation following erythropoietin administration; (2) characterize the chemical mediation of this response; (3) determine the relationship between the changes in the microcirculation during erythropoietic stimulation and suppression and tissue pH and pO2; (4) biochemically verify, quantitate and time the changes in concentrations of mucopolysaccharides under conditions of erythropoietic stimulation and suppression; (5) describe accurately the distribution of the mucopolysaccharides in S1/S1d and W/Wv mice by electronmicroscopic histochemistry; (6) elucidate the interrelationship between erythropoietin, cell coats, and erythropoiesis; and (7) correlate these into a sequence of events that will substantiate, modify or replace our current working hypothesis of the role of the microenvironment in erythropoiesis.